The research proposal presented in this grant application is directed toward the study of the first formed and thus most primitive lymphocytes within a mammalian embryo, in this case mouse. These lymphocytes are produced through tissue culture of the yolk sac removed at nine days of gestation, which is prior to the time the thymus is lymphoid, and harvested at 12 days of gestation, a time after which the thymus is lymphoid in a normal developing mouse embryo. A pilot study which has been carried out indicates that lymphocytes do develop within the yolk sac during the 9- to 12-day period. The first segment of this study will deal with proving that the yolk sac lymphocytes are embryonic by using chromosome analysis, studying the stages in the development of the lymphocytes using light and electron microscopy and determining if and when antibody synthesis begins by using the fluorescent antibody technique. The second segment of the study will deal with culturing pure thymic reticular-epithelial cells and studying the interaction of these cells with primitive yolk sac lymphocytes using light and transmission electron microscopy, scanning electron microscopy and the fluorescent antibody technique.